Multiple Dose Study in Heart Failure of BAY 1067197 (PARSiFAL)
2019年6月19日 更新者：Bayer
A Double Blinded, Placebo Controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics and Acute Cardiovascular Responses of a 7 Day Oral Treatment With the Partial Adenosine A1 Receptor Agonist BAY1067197 in Patients With Chronic Systolic Heart Failure: the PARSiFAL-pilot Study.
This is a study to investigate the safety, tolerability and early effects on cardiac function of the partial A1 agonist BAY1067197 in patients with chronic heart failure.
BAY1067197 will be applied once daily over 7 days in addition to standard therapy including a beta-blocker.
The aim of the study is to assess if a 7 day treatment with BAY1067197 is well tolerated when given on top of standard therapy for heart failure.
Furthermore, the study aims to assess if cardiac function improves in the early course of therapy.
研究概览
研究类型
介入性
注册 (实际的)
31
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 75年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
- Inclusion Criteria:
- Clinical diagnosis of chronic systolic heart failure of ischemic or non-ischemic etiology:(New York Heart Association)NYHA class I-III and treatment with standard pharmacological therapy for the treatment of systolic heart failure including β-blocker ≥ 4 weeks prior to randomization
- Left ventricular ejection fraction ≤ 40%: by any imaging technique within the last 3 months will be accepted for screening purposes but will be verified by baseline CMR(Cardiac Magnetic Resonance Tomography)
- Sinus rhythm for at least 4 weeks prior to randomization
- No planned changes to heart failure related drug therapy for the duration of study drug treatment
- Substantial dysfunctional but viable myocardium as demonstrated by the baseline CMR: Based on a standard 17-segment model (AHA - American Heart Association), 3 or more segments require demonstration of dysfunction (defined by visible assessment of the performing investigator) and viability (defined as < 25% of segment area with scar burden - in patients with CAD (Coronary Artery Disease) or no (i.e. zero) scar burden in patients without CAD [idiopathic CM patient])
- Men or confirmed postmenopausal women or women without childbearing potential.
- Age: 18 to 75 years (inclusive) at the first screening visit.
- Body Mass Index (BMI) :above /equal 18.0 and below/equal 34.9kg/m²
- Exclusion Criteria:
- Atrial fibrillation / atrial flutter within the last 4 weeks prior to randomization or currently persistent/permanent atrial fibrillation / atrial flutter
- Primary valvular disease (severe valvular disease) with planned valve repair or replacement
- Non-idiopathic non-ischemic causes for cardiomyopathy (constrictive, restrictive, or hypertrophic cardiomyopathy; acute myocarditis)
- Listing for heart transplantation and/or anticipated/implanted ventricular assist device Clinically relevant ventricular arrhythmias within the last 2 months (sustained ventricular tachycardia, ventricular flutter or fibrillation), based on either medical history or ICD-testing results (if applicable)
- Unstable cardiac condition, indicated by requirement of IV drug (diuretic, inotrope, etc.) or NYHA IV within 4 weeks prior to randomization
- Coronary revascularization within 4 weeks prior to randomization or if revascularization is anticipated or needed
- Current permanent or intermittent AV-Block > I° or history of AV-Block > I° within six months before enrollment
- PR duration ≥ 300 ms
- Acute Coronary Syndrome (defined as unstable angina [UA], non-ST elevation myocardial infarction [NSTEMI], ST elevation myocardial infarction [STEMI]) within 2 months prior to randomization
- Subjects with untreated hyperthyroidism or hypothyroidism and non-stable thyroid function (intake of stable thyroid hormone substitution allowed)
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
安慰剂比较：安慰剂
|
5 mg / or 10 mg / or 20 mg Placebo for 7 d treatment once daily as oral application
|
|
有源比较器：BAY1067197 (10 mg)
|
10 mg BAY1067197 for 7 d treatment once daily as oral application
|
|
有源比较器：BAY1067197
|
The dose escalation to the second dose step will proceed only if the previous dose step has shown acceptable safety and tolerability 5 mg / or 10 mg / or 20 mg BAY1067197 for 7 d treatment as oral application.
|
|
安慰剂比较：Placebo (10 mg)
|
10 mg Placebo for 7 d treatment once daily as oral application
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of Subjects With Relevant Changes in Heart Rate
大体时间：From the start of study treatment up to Day 29
|
Heart rate was measured by monitor measurements after 30 minutes resting in a supine position.
The relevant changes in heart rate were recorded and analysed.
|
From the start of study treatment up to Day 29
|
|
Number of Subjects With Relevant Changes in Blood Pressure
大体时间：From the start of study treatment up to Day 29
|
Blood pressure was measured by monitor measurements after 30 minutes resting in a supine position.
The relevant changes in blood pressure were recorded and analysed.
|
From the start of study treatment up to Day 29
|
|
Number of Subjects With More than First Degree Atrio-Ventricular (AV) Block
大体时间：After 7 day tratment and day 28
|
A complete standard 12-lead ECG was recorded and evaluated parameters such as heart rate, PR/PQinterval, QRSD interval, QT interval (uncorrected).
Clinically relevant findings in ECG such as a second degree AV-block Mobitz type I (Wenkebach), Mobitz type II - or any third-degree AV block were recorded and reported.
A 24-hour Holter ECG was recorded with a standard Holter ECG recorder for the purpose of detecting AV blocks, no higher degree AV blocks > 1 or clinically relevant effect on HR were observed during Holter monitoring periods.
|
After 7 day tratment and day 28
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
大体时间：Baseline to day 7
|
The change in LVEF between the post and the pre-treatment measurements were analyzed using Bayesian statistics to quantify the difference between BAY1067197 treatment and placebo measured by CMR.
LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart.
|
Baseline to day 7
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma (Cmax) After First Dose of BAY1067197
大体时间：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
Maximum observed BAY84-3174 concentration in plasma, directly taken from analytical data.
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose (Cmax/D) After First Dose of BAY1067197
大体时间：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
Maximum observed drug concentration, directly taken from analytical data, divided by dose.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval (AUCtau) After First Dose of BAY1067197
大体时间：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after the first dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose (AUCtau/D) After First Dose of BAY1067197
大体时间：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau/D is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval divided by dose after the first dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma (Cmax,md) After Multiple Dose Administration During a Dosing Interval
大体时间：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
Cmax,md is defined as maximum observed drug concentration in plasma after multiple-dose administrations during a dosing interval directly taken from analytical data.Geometric mean and %CV were reported.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose (Cmax,md/D) After Multiple Dose Administration During a Dosing Interval
大体时间：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
Maximum observed drug concentration, directly taken from analytical data divided by dose after multiple doses.
Geometric mean and %CV were reported.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 During any Dosing Interval (AUCtau,md) After Multiple Dose Administration
大体时间：Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau,md is defined as area under the plasma concentration time profile from time zero during the dosing interval after multiple-dose administrations and dosing interval was 24 h for both arms. Geometric mean and %CV were reported. |
Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 During any Dosing Interval Divided by Dose (AUCtau,md/D) After Multiple Dose Administration
大体时间：Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau,md/D is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after multiple dose of administrations divided by dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Changes From Baseline for Wall Motion Score Index at Day (WMSI) as Measured by Cardiac Magnetic Resonance at Day 7
大体时间：Baseline to day 7
|
Wall motion score index will cover the changes in wall motion score from baseline also.
|
Baseline to day 7
|
|
Number of Subjects With Clinically Relevant Changes Observed in Echocardiography Parameters
大体时间：Baseline, Day 6 and 15
|
Septal mitral annulus (e' septal), Lateral mitral annulus (e' lateral), E/e' average (average of e' lateral and e' septal), E/e' Lateral ratio, E/e' Septal ratio, Peak early doppler transmitral flow velocity (E), Peak atrial doppler transmitral flow velocity (A), E/A Ratio, Deceleration time (DT), Global longitudinal strain, Cardiac output, Stroke volume, Stroke volume index, Peak systolic tissue Doppler Velocity (Smax), Left ventricular end-systolic volume (LVESV), Left ventricular enddiastolic volume (LVEDV), Left atrial volume index (LAVI), Peak pulmonary systolic pressure (PAPsys).
|
Baseline, Day 6 and 15
|
|
Number of Subjects With Clinically Relevant Changes Observed in Biomarkers
大体时间：Baseline up to Day 15
|
N-terminal prohormone of brain natriuretic peptide (NT-proBNP), renin, mid-region pro-atrial natriuretic peptide (MR-proANP) are biomarkers which show effect on neurohormones.
|
Baseline up to Day 15
|
|
Time to Reach Maximum Observed Concentration of BAY84-3174 in Plasma (tmax) After First Dose of BAY1067197
大体时间：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
Time to reach maximum drug concentration in the measured matrix, directly taken from analytical data
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose per Body Weight (AUCtau,md,norm) After Multiple Dose Administration
大体时间：Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau,md,norm is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after multiple dosing divided by dose per body weight.
The dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose per Body Weight (Cmax,md,norm) After Multiple Dose Administration
大体时间：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
Cmax,md,norm defined as maximum observed drug concentration in plasma after the first dose followed by multiple-dose administrations during a dosing interval divided by dose per body weight.
Geometric mean and %CV were reported.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Time to Reach Maximum Observed Concentration of BAY84-3174 in Plasma (tmax,md) After Multiple Dose Administration
大体时间：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
tmax,md defines as time to reach maximum drug concentration in the measured matrix after multiple dose administrations directly taken from analytical data.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Half-Life Associated With the Terminal Slope (t1/2,md) After Multiple-Dose Administration
大体时间：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
t1/2,md is defiend as time to reach maximum observed drug concentration in plasma after the first dose followed by multiple-dose administrations.
Geometric mean and %CV were reported.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma After First Dose Divided by Dose per Body Weight (Cmax,norm)
大体时间：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
Cmax,norm is defined as maximum observed drug concentration in plasma after the first dose divided by dose per body weight.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose per Body Weight (AUCtau,norm) After First Dose of BAY1067197
大体时间：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau,norm is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval divided by dose per body weight after the first dose.
Dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
赞助
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2014年1月28日
初级完成 (实际的)
2015年1月29日
研究完成 (实际的)
2015年4月2日
研究注册日期
首次提交
2014年1月17日
首先提交符合 QC 标准的
2014年1月17日
首次发布 (估计)
2014年1月20日
研究记录更新
最后更新发布 (实际的)
2019年6月21日
上次提交的符合 QC 标准的更新
2019年6月19日
最后验证
2019年6月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
BAY1067197 (10 mg)的临床试验
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